PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity

Safety and Efficacy of Cyclophosphamide and Ruxolitinib for Graft-versus-host-disease Prophylaxis After Hematopoietic Stem Cell Transplantation With Thymoglobulin Serotherapy in Conditioning Regimen in Patients With Inborn Errors of Immunity

The aim of the current study is to evaluate the efficacy of combined regimen of GVHD prophylaxis with thymoglobulin in conditioning regimen and PTCY with ruxolitinib used after HSCT in patients with inborn errors of immunity (IEI)

Study Overview

• Status: Recruiting
• Conditions: Inborn Errors of Immunity
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Ruxolitinib

Detailed Description

Hematopoietic stem cell transplantation (HSCT) is widely used in inborn errors of immunity (IEI), and risks of graft-versus-host disease (GVHD) remain high. Use of post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis revolutionized the outcomes of HSCT from mismatched related donor (MMRD). Use of ruxolitinib for GVHD prophylaxis demonstrates promising results in adult patients. Another well-known option for GVHD prevention is antithymocyte globulin. To evaluate the efficacy of combination of thymoglobulin with PTCY and ruxolitinib for GVHD prophylaxis, conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, and thiotepa 10 mg/kg or melphalan 140 mg/m2 and GVHD prophylaxis regimen containing cyclophosphamide 50 mg/kg for MMRD, 25 mg/kg for matched unrelated and related donors at days +3, 4 post-HSCT and ruxolitinib at dose 7 mg/m2 from day +5 after HSCT will be used in patients with IEI.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dmitry Balashov, MD, PhD; Phone Number: +74956647091; Email: bala8@yandex.ru
• Study Contact Backup: Name: Alexandra Laberko, MD, PhD; Phone Number: 74952876570; Email: alexandra.laberko@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • HSCT department
    • Contact: Dmitry Balashov, MD, PhD; Phone Number: +74956647091; Email: bala8@yandex.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged ≥ 0 months and < 21 years
2. Patients diagnosed with NBS eligible for an allogeneic HSCT
3. Signed written informed consent signed by a parent or legal guardian

Exclusion Criteria:

Concomitant severe somatic disease associated with an additional risk of severe complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: intervention/treatment; Conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, thymoglobulin 5 mg/kg and thiotepa 10 mg/kg or melphalan 140 mg/m2 GVHD prophylaxis regimen for matched unrelated (MUD) and matched related donors (MRD): Cyclophosphamide (PTCY) 25 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5 GVHD prophylaxis regimen for mismatched related donor (MMRD): Cyclophosphamide (PTCY) 50 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5

Drug: Cyclophosphamide; Cyclophosphamide 25mg/kg (days +3, +4) after HSCT from MUD and MRD Cyclophosphamide 50mg/kg (days +3, +4) after HSCT from MMRD; Drug: Ruxolitinib; Ruxolitinib 7 mg/m2 from day +5 after HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	Events: graft failure, death	1 year after HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of engraftment		100 days
Incidence of early organ toxicity		100 days
Overall survival		1 year after HSCT
Cumulative incidence of acute graft versus host disease		1 year after HSCT
Cumulative incidence of chronic graft versus host disease		1 year after HSCT
Cumulative incidence of graft failure		1 year after HSCT
Cumulative incidence of transplant related mortality		1 year after HSCT
Cumulative incidence of viral infections		1 year after HSCT
Investigation of the concentration of ruxolitinib in the blood To investigate the pharmacokinetics of ruxolitinib	The features of pharmacokinetics in children of different ages	1 month after HSCT

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Investigators: Study Chair: Dmitry Balashov, MD, PhD, National Research Center for Pediatric Hematology, Moscow, Russia

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2023
• Primary Completion (Estimated): November 21, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: IEI-PTCy 2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No